Pancreatic cancer is the fourth most common cause of cancer-related death in the United States. (American Cancer Society Statistics, 2011). Ninety-four percent of patients diagnosed with pancreatic cancer die within 5 years of the diagnosis, giving pancreatic cancer the highest mortality rate of all major cancers. While a fifty-five percent increase in new pancreatic cancer cases is predicted over the next two decades, no early detection methods have been developed.
The most common form of pancreatic cancer is ductal adenocarcinoma (PDAC), which accounts for ninety-five percent of all pancreatic tumors. The vast majority of PDAC patients suffer from significant morbidity from local tumor growth, which include symptoms of abdominal pain, anorexia, nausea, vomiting, and jaundice. Unfortunately, the majority of diagnosed PDAC is not resectable, which limits therapies for local disease control to a combination of radiation and chemotherapy.
Despite the development of new anti-cancer agents, PDAC remains highly refractory to systemically delivered therapies, due in part to (i) impaired drug delivery caused by lack of local vasculature that limits drug distribution within the tumor and (ii) a fibrotic response to the tumor cells that restricts penetration of drug. These factors cannot be overcome by systemic therapies because of limited local residence and dose related toxicities that prevent use of high drug concentrations. For example, gemcitabine therapy has a ten percent response rate, and those regimens that increase response also increase systemic toxicity (e.g., FOLFIRINOX regimen has a thirty-one percent response rate but with greater systemic toxicity). (Conroy, T. et al, New England J. Medicine, 364:1817-25 (2011).
Accordingly, there remains a need for improved methods and devices for cancer therapy, in particular for reducing the problems associated with systemic administration of chemotherapeutic agents to treat tumors. It would be desirable to have better approaches for treating tumors in the pancreas and other intraperitoneal sites, the biliary system, gallbladder, liver, small bowel, and colon.